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Metabolic Syndrome and the Effectiveness of Low-dose Aspirin on Reproductive Outcomes

Nobles, Carrie J.a; Mendola, Paulinea; Mumford, Sunni L.a; Kim, Keewana; Sjaarda, Lindseya; Hill, Micahb; Silver, Robert M.c; Naimi, Ashley I.d; Perkins, Neil J.a; Schisterman, Enrique F.a

doi: 10.1097/EDE.0000000000001019
Reproductive Epidemiology
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Background: Metabolic syndrome is associated with increases in both inflammation and aspirin resistance, but effectiveness of aspirin in improving reproductive health among women with metabolic syndrome is unknown. We evaluated the effectiveness of low-dose aspirin in improving reproductive outcomes across metabolic syndrome score.

Methods: The EAGeR trial randomly assigned 1228 women with a history of pregnancy loss to receive 81 mg aspirin or placebo for up to six menstrual cycles of attempting pregnancy and, if they became pregnant, throughout pregnancy. We assessed components of metabolic syndrome at enrollment, including: waist circumference ≥88 cm, triglycerides ≥150 mg/dl, high-density lipoprotein ≤50 mg/dl, blood pressure ≥130 mmHg systolic or ≥85 mmHg diastolic, and glucose ≥100 mg/dl. We summed components to calculate metabolic syndrome score.

Results: A total of 229 participants (20%) met full criteria for metabolic syndrome, 207 (18%) had two components, 366 (31%) one component, and 372 (32%) no components. Among those without any component of metabolic syndrome, aspirin was associated with 10.7 [95% confidence interval (CI) = 1.2, 20.2] more pregnancies and 13.7 (95% CI = 3.3, 24.0) more live births per 100 couples. Effects were attenuated as metabolic syndrome score increased and we observed no clear effect of aspirin on pregnancy or live birth among women with metabolic syndrome.

Conclusions: Low-dose aspirin is most effective in increasing pregnancy and live birth among women with no or few components of metabolic syndrome. Reduced effectiveness among women with metabolic syndrome may be due to differences in effective dose or aspirin resistance.

From the aEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD

bDepartment of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Bethesda, MD

cObstetrics and Gynecology, School of Medicine, University of Utah, Salt Lake City, UT

dDepartment of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA.

Submitted September 11, 2018; accepted March 22, 2019.

This research was supported by the International Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD; contract numbers HHSN267200603423, HHSN267200603424, and HHSN267200603426); A.I.N. was supported by R01 HD093602.

The authors report no conflicts of interest.

Data sharing: Please see http://grants.nih.gov/grants/policy/data_sharing/ for National Institutes of Health data sharing policy.

Clinical trials registration: ClinicalTrials.gov (no. NCT00467363).

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Enrique F. Schisterman, Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, Bethesda, MD 20892. E-mail: schistee@mail.nih.gov

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